MK-0677 Raised IGF-1 by 84% in Hip-Fracture Patients But Failed to Improve Function
Background
Hip fracture in older adults leads to severe functional decline, and recovery is often incomplete even with rehabilitation. The GH/IGF-1 axis is known to decline with aging, potentially blunting anabolic repair after skeletal trauma. Stimulating endogenous growth hormone secretion was proposed as a strategy to accelerate functional recovery, since IGF-1 is a key mediator of muscle and bone anabolism. MK-0677 (ibutamoren) is an orally active GHSR agonist that mimics ghrelin to stimulate pulsatile GH release, offering a non-injectable means to elevate the GH/IGF-1 axis in elderly patients who are often frail and polymedicated.
Study Design
A placebo-controlled, randomized, double-blind trial enrolled 161 hip-fracture patients aged ≥65 across 13 medical centers in seven countries. Patients were recruited 3–14 days postoperatively (or ≤18 days post-fracture) and randomized to daily oral MK-0677 or placebo for 6 months, with a further 6-month follow-up off treatment. The primary endpoint was change in a panel of functional performance measures from Week 6 to Week 26. Secondary endpoints included the Sickness Impact Profile for Nursing Homes (SIP-NH), ability to live independently, and serum IGF-1 levels measured via ELISA.
Results
MK-0677 produced a robust and statistically significant rise in serum IGF-1: a mean increase of 84% (95% CI = 63–107%) compared with only 17% (95% CI = 8–28%) in the placebo group, confirming target engagement of the GHSR-GH axis.
Serum IGF-1 increased 84% on MK-0677 vs 17% on placebo — yet no statistically significant functional benefit was observed on any primary endpoint.
Despite this strong biomarker response, there were no significant differences between the two arms in improvement of functional performance measures or in the overall SIP-NH score. MK-0677 patients did show greater numerical improvement relative to placebo in 3 of 4 lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, but none of these differences reached statistical significance. The trial's authors noted that high variability in functional outcomes, the absence of a validated pre-fracture baseline, and potentially underpowered sample size all complicated interpretation.
Key Findings
- MK-0677 increased serum IGF-1 by 84% (95% CI 63–107%) vs 17% (95% CI 8–28%) on placebo.
- No statistically significant difference in functional performance measures between MK-0677 and placebo.
- Greater numerical improvement on MK-0677 in 3 of 4 lower extremity functional measures, but not significant.
- No significant difference in overall SIP-NH score between treatment arms.
- 161 hip-fracture patients ≥65 years enrolled across 13 centers in 7 countries.
Why It Matters
The 84% IGF-1 elevation confirms MK-0677 reliably engages its target even in elderly, post-surgical patients — a pharmacokinetically important signal for clinicians and researchers designing GH-axis interventions. However, the disconnect between robust biomarker response and absent functional benefit is a critical caution: raising IGF-1 does not automatically translate into clinically meaningful recovery. For protocol designers stacking MK-0677 with rehabilitation or other anabolic agents in aging populations, this trial suggests that functional outcome measures themselves may be insufficiently sensitive, meaning negative trials may not be true negatives. The 6-month oral dosing in a frail elderly cohort also demonstrates tolerability at the trial level, though granular safety data are not reported in the abstract.
TitrateLab articles covering MK-677
Written by TitrateLab, separately from the study summarized above.
